Targeting CDK‐2 With Novel Indole‐Pyrazole Hybrids: Discovery of Potent Anticancer Agents Supported by Mechanistic and In Silico Studies

Discovery of a novel 1H-pyrazole-3-amine derivative 6h with potent antitumor activity by targeting tubulin and FLT3.

Results suggested that 6h could be regarded as a promising lead compound against tubulin and FLT3 for further investigation.

Design, Synthesis, and Mechanistic Understanding of Thioxothiazole Scaffolds as Possible Apoptotic Inducers and CDK2 Inhibitors in Melanoma

Findings identify compound 11 as a promising selective CDK2‐targeted lead for melanoma therapy as a result of preliminary screening.

Synthesis, characterization, docking and in vitro evaluation of new pyrazole-carboxylate derivatives as antibacterial, anticancer and anti-inflammatory agents

Mechanistic studies indicated that compounds 5c and 5f inhibited cancer cell growth predominantly by inducing apoptosis rather than cell cycle arrest, indicating favourable selectivity.

Synthesis of Novel Benzoxazole–Piperazine Hybrids as Anticancer Leads: Biological, Molecular Docking, and ADMET Evaluations

Cyanopyridine-based derivatives as potent anticancer agents: Integrating in silico analysis and in vitro biological targeting of the EGFR/AKT/MAPK Signaling Cascade.

The increasing global incidence of cancer and the recurrent development of resistance to standard treatments require a rapid development of innovative, multi-targeted chemotherapeutic medicines. This study focused on the strategic design and synthesis of a range of new cyanopyridine derivatives (1a,b-5a,b) targeting the critical oncogenic kinases. The antiproliferative efficacy of these derivatives was assessed against the breast cancer cell line (MCF-7) and the colorectal cancer cell line (HCT116), demonstrating moderate to significant inhibitory activity, with IC50 values ranging from 6.93 to 43.49 μM. Compound 2b emerged as the most selective and potent derivative in the series, showing greater activity against HCT116 cells (IC50 = 7.34 μM) compared to MCF-7 cells (IC50 = 17.55 μM). Experimental investigations demonstrated that compound 2b exerts its anticancer effects by inducing apoptosis and initiating G0-G1 cell cycle arrest. Moreover, compound 2b was identified as an effective inhibitor of key tumor-promoting signaling pathways, including EGFR (IC50 = 0.300 μM), AKT (IC50 = 0.706 μM), ERK (IC50 = 0.143 μM), and p38-MAPKα (IC50 = 0.308 μM). The structural design was validated by molecular docking simulations and molecular dynamics simulations, which revealed favorable binding affinities to the target kinases' active sites. In silico ADME analysis of compound 2b showed favorable drug-like properties, including compliance with the Veber rules and a bioavailability score of 0.55. The combined results underscore the promise of the cyanopyridine scaffold as a framework for developing selective multi-target anticancer medicines.

Synthesis and Evaluation of Novel Piperazine Hybrids as Promising Anticancer Agents

The results revealed that the synthesised derivative 3h has potential binding affinity hence blocking the activity, and the synthesised piperazine derivatives are identified as promising lead compounds for further anticancer optimization.